Prolonged higher dose methylprednisolone<i>versus</i>conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)
Authors: Francesco Salton, Paola Confalonieri, Stefano Centanni, Michele Mondoni, Nicola Petrosillo, Paolo Bonfanti, Giuseppe Lapadula, Donato Lacedonia, Antonio Voza, Nicoletta Carpenè, Marcella Montico, Nicolò Reccardini, Gianfranco Umberto Meduri, Barbara Ruaro, Marco Confalonieri, Gloria Maria Citton, Giulia Lapadula, Chiara Bozzi, Stefano Tavano, Riccardo Pozzan, Alessia Giovanna Andrisano, Mohamad Jaber, Marco Mari, Liliana Trotta, Lucrezia Mondini, Mariangela Barbieri, Luca Ruggero, Caterina Antonaglia, Sara Soave, Chiara Torregiani, Tjaša Bogatec, Andrea Baccelli, Giulia Nalesso, Beatrice Re, Stefano Pavesi, Maria Pia Foschino Barbaro, Antonella Giuliani, Claudia Ravaglia, Venerino Poletti, Raffaele Scala, Luca Guidelli, Nicoletta Golfi, Andrea Vianello, Alessia Achille, Paolo Lucernoni, Anna Talia Gaccione, Micaela Romagnoli, Alessia Fraccaro, Nicola Malacchini, Mario Malerba, Beatrice Ragnoli, Alessandro Sanduzzi Zamparelli, Marialuisa Bocchino, Francesco Blasi, Maura Spotti, Carmen Miele, Federica Piedepalumbo, Ivan Barone, Stefano Baglioni, Meridiana Dodaj, Cosimo Franco, Francesco Andrani, Angelo Mangia, Annalisa Mancini, Laura Carrozzi, Annalisa Rafanelli, Elisabetta Casto, Paola Rogliani, Josuel Ora, Giovanna Elisiana Carpagnano, Valentina Di Lecce, Mario Tamburrini, Alberto Papi, Marco Contoli, Roberto Luzzati, Marta Zatta, Stefano Di Bella, Emanuela Caraffa, Daniela Francisci, Andrea Tosti, Carlo Pallotto, Francesco Giuseppe De Rosa, Alessio Pecori, Marta Franceschini, Massimiliano Carlin, Valentina Orsini, Anna Spolti, Marta Inannace, Teresa Santantonio, Rossella Meli, Sara Sauro, Carlo Fedeli, Elisabetta Mangini, Gianni Biolo, Alessio Nunnari, Antonello Pietrangelo, Elena Corradini, Davide Bocchi, Chiara Boarini, Antonella Zucchetto, Simone Lanini
Journal: European Respiratory Journal (2022)

Background Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7–10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking. Methods We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction ( P aO 2 / F IO 2 ) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14. Results 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P aO 2 / F IO 2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points. Conclusion Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia.